tbuckley/cabot-search huggingface dataset:
Association of <i>DDR1</i> with immune exclusion and outcomes in non-small cell lung cancer.
Authors: Lei Zhang, Ning Lou, Qingxiang Yu, Rui Ma
Journal: Journal of Clinical Oncology (2022)

e20553 Background: Discoidin domain receptor 1 (DDR1) is a collagen receptor with tyrosine kinase activity. Although DDR1 has been reported to implicated in cancer progression and metastases, the underlying mechanism remains poorly characterized and its prognostic value is also contradictory in non-small cell lung cancer (NSCLC). Methods: Clinical and DDR1 mRNA expression data of 1925 patients with NSCLC were obtained from 14 publicly available datasets utilizing an online tool KM-plotter. All patients were split into 2 groups by median expression of DDR1. The Kaplan-Meier curve and log-rank test, and Cox regression analyses were used to examine the association between DDR1 expression and overall survival (OS). The table shows 48 immune-regulatory genes classified into 4 signatures associated with activated T cells, immune cytolytic activity, and antitumor immunity. Expression data of these genes for 994 patients with NSCLC were gathered from the TCGA Pan-Cancer Atlas. Abundance data of various immune cell types in tumor microenvironment for the TCGA patients were inferred using xCell, and then immune infiltration extent was calculated as immune score. Associations of DDR1 with immune genes expression and immune score were determined with Spearman rank correlation. Results: DDR1 overexpression was significantly associated with inferior OS in this large-scale cohort (median, 62 vs 78.5 months; hazard ratio [HR], 1.16; 95% CI, 1.02-1.31; P = .02). Of note, multivariable Cox model indicated DDR1 overexpression was an independent risk factor for OS (HR, 1.41; 95% CI, 1.01-1.98; P = .046), controlling for potential confounders (histology, stage, sex, and smoking history). Of the 48 immune-regulatory genes, 44 (92%) showed significant negative correlations with DDR1 expression (all P &lt; .05), implying the role of DDR1 in decreasing immune infiltration into tumor microenvironment. Further, higher immune score was observed in tumors underexpressing DDR1 (correlation coefficient, -0.44; P &lt; .001), more directly demonstrating the link between DDR1 and immune infiltration. Conclusions: To our knowledge, this is the largest study to evaluate the prognostic role of DDR1 expression in NSCLC. Our results suggest that DDR1 overexpression may predict poor outcomes and a possible mechanistic explanation regarding this role may be immune exclusion instigated by DDR1. Thus, targeting DDR1 expression to abrogate immune exclusion warrants further investigation.[Table: see text]
Self-identification of gender and race/ethnicity in hematology and oncology journal editorial boards: What is the state of diversity?
Authors: Ivy Riano, Shruti Rajesh Patel, Inas Abuali, Angela Ai, Gabriella Geiger, Jacqueline Pimienta, Adriana Ramirez Roggio, Natasha Dhawan, Nazli Dizman, Alexandra Lizette Salinas, Narjust Duma
Journal: Journal of Clinical Oncology (2022)

11058 Background: Underrepresentation of women and minorities persists in many aspects of the scholarly publication process as demonstrated by our initial findings presented at ASCO21. Having a gender-balanced and diverse editorial team promotes collaborative work and decreases the publication bias against women. In our initial study, gender and race/ethnicity were determined based on publicly available data. We aimed to add to our study by asking editors to self-report their gender and race to assess the diversity of editors at leading hematology and oncology journals by self-reporting. Methods: We identified 60 journals in oncology, hematology, radiation oncology, and surgical oncology with the highest impact factors. Editors-In-Chief (EiC) and Second-In-Command (SiC) editors (such as deputy, senior and associated editors) were included in the analysis. A demographic survey assessing gender, race/ethnicity, age, and job characteristics was sent to 793 participants via email. Data were analyzed with R software. Results: A total of 66 out of 793 editorial board members responded to the survey. Gender breakdown of respondents was 36 (54.5%) men and 30 (45.8%) women. Most respondents were between the ages of 40 and 60 (69.7%). Thirty-eight (57.6%) of the editors had ≤5 years of editorial experience. Of the 66 respondents, 44 (66.7%) self-identified as non-Hispanic white, followed by 14 (21.2%) as Asian and 3 (4.5%) as Hispanic. Only 1/66 (1.5%) editors self-identified as Black or Native Hawaiian/Other Pacific Islander, and 1/66 (1.5%) did not identify themselves with a racial group. Conclusions: Underrepresented groups in medicine (URM) and women occupied a minority of leadership roles on editorial boards in high-impact hematology and oncology journals. Notably, this study provides new insights into editorial board diversity by using self-reporting as a primary methodology. Limitations of the cross-sectional study is that URM and women are more likely to respond to surveys on diversity, equity, and inclusion potentially skewing the results. Diversity in editorial boards not only can enhance scientific discovery by encouraging submissions from researchers with diverse backgrounds but also promotes career advancement for women and URM.[Table: see text]
Outcomes of appendiceal cancer treated at a state peritonectomy service.
Authors: Madeleine Cornelia Strach, Nabila Ansari, Cherry Koh, Michael Solomon, Lisa Horvath, Kate Mahon
Journal: Journal of Clinical Oncology (2022)

3629 Background: Appendiceal cancers (AC) are rare with varied prognosis. Nomenclature refined by the WHO 2019 classification is: appendiceal mucinous neoplasms (AMNs), adenocarcinomas (AA) including mucinous (MAC), not otherwise specified (ANOS), signet ring (SRC) and goblet cell (GCA), and neuroendocrine tumours (NET). Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS+HIPEC) is the definitive treatment. The role of chemotherapy remains unclear with conflicting outcomes and there is need to delineate the optimal regimen in different disease settings. The aim of this study was to evaluate AC treatment and clinical outcomes by the WHO 2019 classification and analyse the impact of perioperative chemotherapy. Methods: We reviewed prospective data from the database at an Australian state peritonectomy service, Apr 2017-Dec 2021. Variables included demographics, tumour characteristics, treatment details and survival outcomes. Analysis was by the Kaplan-Meier method using the log-rank test for statistical comparison (SPSSv27). Results: 115 patients (of 207 referred) with confirmed AC proceeded to CRS. Histopathology comprised 49 AMNs (43%), 62 (63%) AA, 3 SRCs and 1 NET. The mean age was 56y (21-78), 53% female. 94% had CRS+HIPEC (Mitomycin 85%). 70% had cytoreductive score 0. The median peritoneal cancer index was 23 (0-39). 20 (17%) had localised (M0) disease, 10 acellular mucin (M1a) and 85 (74%) metastases (M1b/c). 71% were lymph node negative (N0). 40% had chemotherapy (oxaliplatin/5-fluorouracil 57%). 8 of 15 who had molecular testing had a KRAS mutation. Median follow-up was 26m (1.9-167). The table shows univariate survival analysis. Conclusions: This is the first study evaluating outcomes of perioperative chemotherapy for AC in a cohort of patients since the WHO 2019 classification. MAC have worse survival compared to ANOS, but similar to GCAs. Peritoneal acellular mucin has a similarly improved prognosis to patients with no peritoneal disease compared to those with cellular disease. Chemotherapy demonstrated worse survival compared to no chemotherapy, also seen in the literature and likely influenced by selection of more aggressive disease. There is a need to develop biomarkers and better treatments to improve the survival of these patients. Further multivariate analysis for prognostic and predictive factors is planned.[Table: see text]
Severe irAEs in patients with immune checkpoint inhibitor therapy: Experience in a Mexican cancer center.
Authors: Diana Bonilla Molina, Cecilia Nehmad, Juan Manuel Tovar Cabrera, Ervin Saúl Enciso López, Efrain Isaias Camarin Sanchez, Daniela Shveid Gerson, Benigno Rodriguez, Omar Serrano Villamayor, Lorena López Zepeda, Yazmin Carolina Blanco Vazquez, Christian Patricio Camacho Limas, José Fabián Martínez-Herrera, Guillermo Olivares, Raquel Gerson Cwilich
Journal: Journal of Clinical Oncology (2022)

e14559 Background: A relationship has been found between a better response to treatment and the presence of irAEs. Different potential factors for developing them have been described, including the type of immunotherapy and their combination. Rare (&lt; 1%) and potentially life-threatening irAEs have been reported, which due to severity lead to treatment discontinuation, and a prolonged effective response is seen in these patients if they survive the irAE. Methods: Observational study in patients with solid tumors who received treatment with immune checkpoint inhibitor and their characteristic, that presented irAEs grade 3 and 4 using the CTCAE version 4, from January to December 2021 in a Mexican cancer center. Results: irAEs grade 3 or 4 were observed in 7 (5.6%) of 125 patients, with an age range of 60 to 69 years, most of the patients had a diagnosis of metastatic melanoma (43%) and secondly urothelial carcinoma with 29%. The predominant treatment was pembrolizumab monotherapy (56%), with an average of 5 applications after those who presented irAEs. The rare irAEs presented were myocarditis (2.4%), myositis (1.6%), myasthenia gravis and interstitial nephritis, both with 1%. 70% of these patients were managed with three boluses of methylprednisolone and subsequently prednisone 1 mg/kg as maintenance. The median appearance of these irAEs was 72 days. Myocarditis and myositis had an earlier onset with an average of 32 days. One of the seven patients presented myasthenia gravis, myositis and myocarditis concomitantly, with complete response of the neoplasia, however, due to the prolonged use of immunosuppressants to control irAEs, the disease recurred at 7 months. Two of the three patients with myocarditis had a complete response and remain disease free. 57% survived more than 90 days, of which 75% are still alive. Conclusions: Among the 125 patients who received an immune checkpoint inhibitor in our cancer center in 2021, the most prevalent serious irAE was myocarditis, with a higher incidence than that reported by other centers, and a prolonged therapeutic response was found in the patients who presented it.
Emotion and symptom-focused engagement (EASE): A multisite randomized controlled trial of an intervention for individuals with acute leukemia.
Authors: Kyle Fitzgibbon, Carmine Malfitano, Anne Rydall, Breffni Hannon, Harriet Richardson, Aaron David Schimmer, Camilla Zimmermann, Gary Rodin
Journal: Journal of Clinical Oncology (2022)

TPS7072 Background: Acute leukemia (AL) is characterized by rapid symptom onset requiring urgent hospitalization and initiation of intensive treatment with high mortality. Despite this, there is scant research on its psychological and physical impacts and even less on interventions to alleviate them [Bryant 2016]. We conducted a longitudinal study showing substantial physical and psychological distress in these patients [Rodin 2013; Zimmermann 2013; Nissim 2013; Nissim 2014; Gheihman 2016; Rodin 2018a; Shaulov 2019]. Despite this distress, we observed a lack of referrals for specialized psychosocial and palliative care. Based on these findings, we developed an integrated psychosocial and early palliative care (symptom control) intervention, Emotion And Symptom-focused Engagement (EASE), for AL [Rodin 2015]. In a subsequent randomized phase II trial of EASE in patients newly diagnosed with AL, we demonstrated its feasibility and found preliminary evidence that it reduces physical and psychological distress compared to usual care [Rodin 2020]. EASE includes: i) an 8-week manualized psychotherapy intervention tailored to AL to prevent and treat psychological symptoms through: supportive counselling and trauma-focused cognitive-behavioural therapy; and emotional assessment and affect modulation; ii) 4-week systematic screening of physical symptoms with automatic referrals to palliative care for the management of moderate to severe symptoms. Methods: We are conducting a multi-centre randomized controlled phase III trial of 266 AL patients comparing EASE to usual care in collaboration with the Canadian Cancer Trials Group at Princess Margaret Cancer Centre, Sunnybrook Health Sciences, Kingston Health Sciences and the Ottawa Hospital in Ontario, Canada. Patients are newly diagnosed with acute myeloid leukemia or acute lymphoblastic leukemia and randomized within two weeks of hospital admission for induction chemotherapy with curative intent. Patients randomized to EASE will receive psychological support from a trained mental health clinician for 8 weeks and will be assessed for physical symptoms twice weekly until discharged from hospital. Moderate to severe physical symptoms will trigger a referral to a symptom-control team for symptom management. The symptom-control team consists of a physician and nurse with expertise in symptom control and other professionals as needed. All participants will be assessed for physical symptom severity, psychological distress, quality of life and satisfaction with care at baseline, 4, 8, 12 weeks, 6 and 12 months. Hypotheses will be tested using multilevel modeling (MLM) with maximum likelihood estimation, conducted as intention-to-treat analyses. The DMC last reviewed the trial in April 2021 and suggested that the trial continue as planned. Clinical trial information: NCT04224974.
High-definition PCR (HDPCR) detection of DNA and RNA variants in non-small cell lung cancer (NSCLC) samples.
Authors: Gregory J. Tsongalis, Bryan Leatham, Katie McNall, Hari Subramanian, John G Alvarado, Lucien Jacky, Dominic Yurk, Donald Green, Aditya Rajagopal, Jerrod Schwartz
Journal: Journal of Clinical Oncology (2022)

e20603 Background: Digital PCR (dPCR) is an emerging technology platform for detecting genomic variants in cancer genomes due to its high sensitivity and fast time to results compared to sequencing. However, translational oncology applications often require the measurement of more biomarkers than there are color channels available on dPCR platforms. One approach to address this limitation with dPCR is to split a sample across many wells and profile a subset of variants in each well. For input-limited samples, however, this results in fewer molecules being profiled in each dPCR well, resulting in a reduction in sensitivity and fewer patient samples processed per instrument run. ChromaCode has developed a research use only (RUO) digital High Definition PCR (HDPCR) NSCLC assay, for multiplexed detection of 14 DNA variants and 15 RNA fusion variants relevant in non-small cell lung cancer samples. The assay is constructed using both amplitude modulation and multi-channel resilient signal encoding methods. Amplitude modulation enables different variants to generate a distinguishable signal at different intensity levels in a single color channel, allowing for multiple targets to be detected within that single-color channel. In addition, resilient encoding generates a signal in more than one color channel to create a form of error detection in the assay design. Methods: Assay benchmarking was performed using over 500 contrived human biological FFPE samples, consisting of synthetic DNA or RNA variants spiked into a background matrix of FFPE-extracted DNA or RNA; over 500 contrived human biological plasma samples, consisting of synthetic DNA or RNA variants spiked into a background matrix of plasma-extracted cell free DNA or RNA; and residual human biological FFPE and plasma NSCLC samples that were previously characterized using a targeted sequencing workflow. The samples were tested using the HDPCR NSCLC assay on the QuantStudio Absolute Q Digital PCR system, and data analysis was performed with custom analysis algorithms. Results: For the more than 500 contrived FFPE and plasma samples, the HDPCR NSCLC assay had high overall agreement with expectation across a range of mutant allele fractions for both DNA and RNA analytes (≥99% PPA and ≥99% NPA). For a set of N = 25 residual human biological FFPE samples, the assay was also highly concordant (100% PPA and 99% NPA) with a targeted panel sequencing comparator. The hands-on workflow time from isolation start to analysis complete was &lt; 24 hours. Conclusions: The HDPCR NSCLC assay is a robust RUO tool for the sensitive and rapid detection of commonly targeted variants relevant to NSCLC samples. This technology could complement sequencing assays when there is a need for a rapid turnaround time or there are limited amounts of isolated nucleic acid.
Retrospective study on the safety and efficacy of pyrotinib in the treatment of HER2-positive non-breast advanced solid tumors.
Authors: Jianzheng Wang, Baiwen Zhang, Xiaojiao Cheng, Qingli Li, Huifang Lv, Caiyun Nie, Beibei Chen, Weifeng Xu, Jing Zhao, Yunduan He, Shuiping Tu, Xiaobing Chen
Journal: Journal of Clinical Oncology (2022)

e15064 Background: Human epidermal growth factor receptor 2 (HER2) is a member of the ErbB family and a key oncogene in solid tumors. Pyrotinib has been approved for the treatment of HER2-positive, recurrent or metastatic breast cancer. However, there are very few clinical studies on pyrotinib in other HER2-positive solid tumors. Therefore, more clinical evidence is urgently needed to guide pyrotinib-based therapy in HER2-positive non-breast advanced solid tumors. Methods: We retrospectively analyzed HER2-positive non-breast advanced solid tumors patients with HER2 amplification or mutations who were treated with pyrotinib-based therapy in Henan Cancer Hospital between July 1, 2019 and December 2, 2021. In this study, 25 eligible patients were included with 16 patients with lung cancer, 6 with gastric cancer, 2 with colorectal cancer and 1 with cholangiocarcinoma. The primary end point was progression-free survival (PFS). Results: The median PFS and overall survival (OS) were 188 days (95% CI: 83–NA days) and 250 days (95% CI: 188–NA days), respectively. 16 patients with lung cancer and 6 patients with gastric cancer had a median PFS of 204 days (95% CI: 55–NA days) and 142 days (95% CI: 83–NA days), respectively. The median OS was 366 days (95% CI: 248–NA days) in patients with lung cancer and 179 days (95% CI: 90–NA days) in patients with gastric cancer. Patients receiving &gt; 3 lines of therapies had a numerically lower median PFS and OS than those receiving≤ 3 lines of treatments (PFS:188 vs 204 days, p=0.92; OS:188 vs 366 days, P = 0.43). All 25 patients were available for efficacy evaluation. The objective response rate (ORR) was 24% and disease control rate (DCR) was 68%. The ORR for lung cancer was 25% and for gastric cancer was 16.7%. In addition, the DCR for lung cancer was 62.5% and for gastric cancer was 66.7%. Moreover, patients receiving≤3 lines of treatments had a numerically higher ORR and DCR than those receiving &gt;3 lines of treatment (ORR:35.7% vs 9.1%,p=0.18; DCR:71.4% vs 63.6%, P＞0.99). The most common treatment-related adverse events (TRAEs) were diarrhea (84%), but only 3 (12%) patients reported grade 3 diarrhea which could be well controlled. Conclusions: These results indicated that pyrotinib-based therapy exhibited good anti-tumor activity and acceptable safety profile in HER2-positive non-breast advanced solid tumors. This retrospective study is a pilot study aimed at promoting larger-scale studies to further clarify the safety and efficacy of pyrotinib in the treatment of non-breast solid tumors. Keywords: pyrotinib, HER2-positive, solid tumor, retrospective study, advanced solid tumors.
Real-world analysis of use of lenvatinib in differentiated thyroid cancers.
Authors: Zoya Peelay, Shruti Pathak, Vijay Maruti Patil, Kumar Prabhash, Vanita Noronha, Nandini Sharrel Menon
Journal: Journal of Clinical Oncology (2022)

e18075 Background: Lenvatinib is one of the approved treatments for radioiodine refractory differentiated thyroid cancers. However, there is very limited data from India on real-world efficacy and adverse events of Lenvatinib and hence this analysis was performed. Methods: This was a retrospective analysis in which patients of radioiodine refractory differentiated thyroid cancer as per the select study criteria who received lenvatinib were selected for the study over the last 4 years. The baseline demographic characteristics, adverse events of lenvatinib, the date of progression and the date of overall survival (OS) were extracted from the electronic medical records (EMR) of the Tata Memorial Hospital. SPSS version 20 was used for analysis. Results: Thirty patients were identified. The median age was 54.5 years (25-77). The male: female ratio was1:1. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0-1 in 21(70%), 2 in 4(13.3%) and 3 in 5(16.7%). The thyroid status was hypothyroid in 10 patients (33.3%), euthyroid in 12(40%) and hyperthyroid in 8(26.7%). In 5 patients it had to be stopped because of toxicity, these were proteinuria in 2, a hand-foot syndrome in 2 and diarrhoea in 1. The response rate was 56.7% (n = 17). The median progression-free survival (PFS) on lenvatinib was 366 days(95%CI 170.3-561.67) and the 2 year PFS was 29.3% (standard error 12.1) The median overall survival (OS) on lenvatinib was 411 days (95%CI 95.5-726.6). The 2 year OS was 38.8% (standard error -12.5%) and 5 year OS was 14.6% (standard error 12.1). Conclusions: In the real world lenvatinib provides a 2 year PFS and OS of 29.3% and 38.8% which is lower than that reported in the pivotal SELECT study.
Identifying potential glycoproteomic biomarkers for diagnosis of colorectal cancer (CRC).
Authors: Klaus Lindpaintner, Khushbu Desai, Gege Xu, Rachel Rice, Alyn Castellanos, Danie Serie, Alan Mitchell
Journal: Journal of Clinical Oncology (2022)

e15529 Background: Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in both men and women in the United States. Colorectal cancer (CRC) affects men and women of all racial and ethnic groups and is most often found in people who are 50 years old or older. To aid diagnosis and improve screening for CRC, this study focuses on identifying glycoprotein biomarkers using blood serum. Methods: Novel methods including liquid-chromatography/mass-spectrometry (LC-MS) with in-house peak integration software PB-Net were used to identify glycoprotein biomarkers by analyzing blood serum. Samples were sourced from different biorepositories including 245 CRC, 38 adenoma and 196 healthy controls. The data were split into 75% training and 25% hold-out test set for multivariable predictions. Statistical analysis was performed on normalized data to identify potential biomarkers differentiating adenoma and different stages of CRC samples from the healthy controls. Results: There were 419 significantly differentially expressed glycopeptides/peptides from comparisons between CRC and adenoma samples against the healthy control samples with an FDR &lt; 0.05. A subset of these biomarkers were assessed, generating a 21-biomarker multivariable classifier model. We observed a test set AUC of 0.926, and the sensitivity for all stages of CRC was 90% (87% early stage, 92% late stage). Notably, sensitivity for adenomas was 79%, a large improvement upon the state of the art in adenoma diagnosis. Conclusions: Identification of these key glycopeptides/peptides in blood serum could prove to be a promising non-invasive diagnostic tool that can help improve screening and aid in early detection of advanced adenomas and CRC.